Antiinflammatory and antiatherogenic effects of the NF-κB inhibitor acetyl-11-Keto-β-boswellic acid in LPS-challenged ApoE-/- mice

Abstract

OBJECTIVE - In this article, we studied the effect of acetyl-11-keto- β-boswellic acid (AKβBA), a natural inhibitor of the proinflammatory transcription factor NF-κB on the development of atherosclerotic lesions in apolipoprotein E-deficient (apoE) mice. METHODS AND RESULTS - Atherosclerotic lesions were induced by weekly LPS injection in apoE mice. LPS alone increased atherosclerotic lesion size by ≈100%, and treatment with AKβBA significantly reduced it by ≈50%. Moreover, the activity of NF-κB was also reduced in the atherosclerotic plaques of LPS-injected apoE mice treated with AKβBA. As a consequence, AKβBA treatment led to a significant downregulation of several NF-κB-dependent genes such as MCP-1, MCP-3, IL-1α, MIP-2, VEGF, and TF. By contrast, AKβBA did not affect the plasma concentrations of triglycerides, total cholesterol, antioxidized LDL antibodies, and various subsets of lymphocyte-derived cytokines. Moreover, AKβBA potently inhibited the IκB kinase (IKK) activity immunoprecipitated from LPS-stimulated mouse macrophages and mononuclear cells leading to decreased phosphorylation of IκBα and inhibition of p65/NF-κB activation. Comparable AKβBA-mediated inhibition was also observed in LPS-stimulated human macrophages. CONCLUSION - The inhibition of NF-κB activity by plant resins from species of the Boswellia family might represent an alternative for classical medicine treatments for chronic inflammatory diseases such as atherosclerosis. © 2008 American Heart Association, Inc.